PXD004973

PXD004973 is an original dataset announced via ProteomeXchange.

Title	Spatiotemporal proteomic profiling of Huntington's disease mice reveals widespread loss of protein function
Description	Huntington's disease (HD) is characterized by the aggregation of polyglutamine-expanded huntingtin (HTT), proceeding from soluble oligomers to end-stage inclusions. The molecular mechanisms of how protein aggregation leads to neuronal dysfunction are not well understood. We employed mass spectrometry-based quantitative proteomics to dissect spatiotemporal mechanisms of neurodegeneration using the R6/2 mouse model of HD. We show that extensive remodeling of the soluble brain proteome correlates with changes in insoluble aggregate formation during disease progression. In-depth characterization of HTT inclusion bodies uncovered an unprecedented complexity of several hundred proteins. Sequestration to inclusions was dependent on protein expression levels and the presence of aggregation-prone amino acid sequence features, such as low-complexity regions or coiled-coil domains. Overexpression of several sequestered proteins ameliorated HTT toxicity and modified the aggregation behavior in an in vitro model of HD. Our study provides a comprehensive and spatiotemporally-resolved proteome resource of HD progression, indicating that widespread loss of protein function contributes to aggregate-mediated toxicity.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:10:18.222.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-09-14 23:59:46	ID requested
1	2017-11-24 08:38:34	announced
⏵ 2	2024-10-22 04:10:19	announced	2024-10-22: Updated project metadata.

Hosp F, Guti, é, rrez-, Á, ngel S, Schaefer MH, Cox J, Meissner F, Hipp MS, Hartl FU, Klein R, Dudanova I, Mann M, Spatiotemporal Proteomic Profiling of Huntington's Disease Inclusions Reveals Widespread Loss of Protein Function. Cell Rep, 21(8):2291-2303(2017) [pubmed]

10.1016/j.celrep.2017.10.097;

curator keyword: Biological, Biomedical

submitter keyword: Huntington's disease / inclusion bodies / neurodegeneration / quantitative proteomics

Matthias Mann
contact affiliation	Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany Department of Proteomics and Signal Transduction
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/11/PXD004973

PRIDE project URI

• PRIDE
  1. PXD004973
     1. Label: PRIDE project
     2. Name: Spatiotemporal proteomic profiling of Huntington's disease mice reveals widespread loss of protein function